Promoter Methylation of Txnip and Adrb3 Genes: Potential Blood-Based Biomarkers for Metabolic Syndrome Publisher Pubmed



Dizghandi S E ; Mostafapour S ; Khodabandehloo F ; Alani B ; Saremi L ; Kenarangi T ; Mosallaei M ; Rezvankhah B
Source: Molecular Biology Reports Published:2026

Abstract

Background: Many studies have indicated that epigenetic mechanisms, particularly DNA methylation, play an important role in regulating genes involved in glucose and lipid metabolism, oxidative stress, and energy homeostasis. Among these, TXNIP and ADRB3 are key metabolic regulators linked to insulin signaling, adipose tissue function, and energy expenditure. This study aimed to evaluate promoter methylation levels of TXNIP and ADRB3 in individuals with metabolic syndrome compared with healthy controls and to investigate their associations with clinical and biochemical parameters. Methods: A total of 95 patients with metabolic syndrome and 95 age- and sex-matched healthy controls were enrolled. Genomic DNA was extracted from whole blood, and promoter methylation levels of TXNIP and ADRB3 were quantified using the MethyQESD method followed by quantitative real-time PCR. Results: TXNIP promoter methylation was significantly lower in patients compared with controls (19.59 ± 17.42 vs. 38.77 ± 17.57, P < 0.001), whereas no significant difference was observed for ADRB3 methylation (P > 0.05). TXNIP showed good diagnostic performance for metabolic syndrome (AUC = 0.837, P < 0.001). In patients, TXNIP methylation decreased progressively with increasing FBS, while ADRB3 methylation showed an opposite trend (P < 0.001 for both). TXNIP methylation was positively correlated with HDL-C, whereas ADRB3 methylation showed negative correlation with HDL-C and a positive correlation with BMI and waist circumference. Conclusions: Promoter methylation of TXNIP and ADRB3 was associated with metabolic syndrome-related traits. TXNIP hypomethylation showed strong diagnostic potential, while ADRB3 methylation was shown to be linked to disease-related metabolic parameters, indicating a role in disease severity rather than classification. © The Author(s), under exclusive licence to Springer Nature B.V. 2026.